SKIN COLLAGEN AND THICKNESS IN ACROMEGALY AND HYPOPITUITARISM

The thickness of the forearm skin and its collagen content and density were measured in a group of patients with acromegaly and hypopituitarism. In acromegaly the total content, thickness and collagen density were all increased. There was a smaller and less consistent increase in percentage collagen content. In hypopituitarism total skin collagen and thickness were both decreased and collagen density and percentage collagen content remained normal.     

REDUCTION OF SKIN COLLAGEN WITH INCREASED SKIN THICKNESS IN POSTMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS

Thirty postmenopausal women with rheumatoid disease were investigatedwith skin biopsies and radiological measurements of skin thickness.When compared with menopausal-age-matched controls, the rheumatoidpatients had significantly reduced skin collagen content andincreased skin thickness. KEY WORDS: Skin, Rheumatoid arthritis, Postmenopausal     

PENICILLAMINE IN RHEUMATOID ARTHRITIS: WOUND HEALING, SKIN THICKNESS AND OSTEOPOROSIS

D-Penicillamine alters the normal metabolism of collagen byinhibiting cross-linking and protein synthesis. This could affectwound healing, accelerate skin thinning and possibly exaggeratethe osteoporosis of rheumatoid disease. The mean time to wound healing after 42 orthopaedic surgicaloperations in 21 patients treated with penicillamine was 19.8(±13.1) days. Compared with an earlier study, these resultssuggest that the drug has a comparable effect on wound healingto corticosteroids given for three years. Skinfold thickness over the fourth metacarpal of the dominanthand was measured in 28 cases before and during penicillaminetreatment. There was a significant decrease both in the firstand second four-month periods of treatment (P<0.005 and P<0.01).Corticosteroids in constant dose did not have an additive effect. In view of the wound healing findings the significance of theseresults must await further sequential measurements. The normal progression of osteoporosis over three years wasdocumented in 70 patients who had not received penicillamine.Penicillamine reversed this trend in 35 patients after one yearof treatment (P<0.005). The results confirm that the osteoporosisis related to disease severity rather than drug therapy. ^*Paper read at the Annual Meeting of the British Associationfor Rheumatology and Rehabilitation, London April 1977     

ULTRASOUND MEASUREMENT OF SKIN THICKNESS IN SYSTEMIC SCLEROSIS

Sclerotic skin change in systemic sclerosis (SSc) usually accompaniesincreased skin thickness. In order to quantify the cutaneouschanges and to clarify the changes in the ‘uninvolved’skin in systemic sclerosis (SSc), we measured the skin thicknesson the chest, the forearms and the hands of 79 patients withSSc and 81 healthy controls with a B-mode ultrasound (30 MHz)apparatus. The thickness of the ‘uninvolved’, aswell as the ‘involved’ skin in patients with SScwas significantly greater than that of healthy controls. Increasedskin thickness on the forearms and/or the hands showed a 64.6%sensitivity and a 100% specificity for SSc. These results indicatedthat the skin which appears to be ‘uninvolved’ inpatients with SSc is already pathologic, as shown by increasedthickness. Moreover, measurement of skin thickness may be beneficialin the diagnosis of this disease at an early stage. KEY WORDS: Systemic sclerosis, Skin thickness, ‘Uninvolved’ skin, Ultrasound measurement     

ACID GLYCOSAMINOGLYCANS IN MYXOEDEMA

Acid glycosaminoglycans were measured in the tissues of a virtually untreated 83-year-old woman with myxoedema. Intercellular oedema was demonstrated histologically in the tongue, myocardium, striated muscles, and in the skin. Tissue oedema was absent in two female control patients. All tissues from the patient with myxoedema, apart from the stomach, showed high concentrations of hyaluronic acid, but there was no consistent elevation of chondroitin-4,6-sulphate, heparan sulphate or dermatan sulphate. The accumulation of hyaluronic acid might contribute to the oedema formation in myxoedema.     

MATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING

Six hundred and forty-three neonates from mothers with Graves' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6.0% (three of 50), 0.3% (one of 350), 1.7% (two of 117) and 0.0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P less than 0.01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect, if any.     

SOTALOL IN HYPERTHYROIDISM

Ten hyperthyroid patients were studied before and after 2 weeks' β-adrenoceptor blockade with sotalol. The following variables were measured: resting pulse rate, blood pressure, weight, thyroid hormone levels, plasma lipids, alkaline phosphatase, plasma glucose and insulin responses to oral glucose, bromsulph-thalein retention and the 24-h urinary excretion of calcium, hydroxyproline, creatine and creatinine. Sotalol produced a significant fall in pulse and blood pressure. Weight loss continued during treatment. No metabolic changes of any consequence were found. It is concluded that sotalol should not be used as the sole treatment of a patient with hyperthyroidism.     

NOCTURNAL NATRIURESIS IN HYPERTHYROIDISM

We measured urine flow and the renal excretion of total solute, sodium, potassium and calcium in eleven patients with hyperthyroidism before and after treatment. Mean nocturnal sodium excretion was significantly greater (P < 0·05) during hyperthyroidism and was unaccompanied by any significant alterations in day time or 24-h values. As a result of this nocturnal natriuresis in hyperthyroidism significant changes were noted in the ratios of day/night sodium excretion (P < 0·005) and urinary flow (P < 0·05). The change in ratio of day/night sodium excretion resulting from treatment of hyperthyroidism was shown to correlate significantly with the change in plasma total triiodothyronine (r=0·73, P < 0·01). Twenty-four hour urinary calcium output was significantly greater (P < 0·02) in hyperthyroidism but there was no significant alteration in the day/night pattern of excretion.     

SERUM TRIIODOTHYRONINE AND HYPERTHYROIDISM IN A POPULATION SAMPLE OF WOMEN

The serum T3 assay has been regarded as the most sensitive single test for hyperthyroidism although impaired conversion of T4 to T3 in non-thyroidal illness (NTI) might decrease its diagnostic sensitivity. The present report gives experience from the T3 assay in middle-aged females under conditions similar to those in a general health survey. The assays were performed during two periods with an interval of six years. In 1974–75 we studied a representative sample (n= 1283) of women of ages 44, 52, 56, 60 and 66 years in Göteborg, Sweden. Individuals with serum T3 concentration > mean + 2·5 SD were selected for a follow-up study (n= 21). Of 16 individuals with no previous thyroid disease and no present treatment with thyroid hormones or oestrogens, 14 were subjected to a TRH-stimulation test giving a normal TSH response in 10 cases having T3 concentrations up to mean + 3·5 SD. Four women with serum T3 concentration ≥ mean + 3·5 SD had previously unrecognized autonomous function thyroid function, of whom two developed hyperthyroidism after two years. The original population sample was reinvestigated after six years in 1980-81 (n= 1138) together with an additional sample of women giving a total sample of 1422 women of ages 26, 38, 50, 58, 62, 66 and 72 years. Of the females studied in 1974–75 eight had developed hyperthyroidism between the two studies; three of these had raised serum T3 at the investigation in 1974–75. No case of hyperthyroidism had been missed by the T3 assay in the 1974–75 study. Of individuals with serum T3≥mean + 2·5 SD selected for a follow-up (n= 29) at least five were found to have previously unrecognized thyroid autonomy. We found a raised serum T3 to be associated with hyperthyroid (n= 2) and euthyroid GRAVES' disease, autonomously functioning thyroid adenoma(s), possible painless subacute thyroiditis, possible thyrotoxicosis factitia, diminished thyroid reserve and thyroid substitution therapy. Since we did not correct for variations in protein binders a number of individuals with oestrogen-associated rise of total T3 were identified, but the rises were usually modest. The incidence of hyperthyroidism for the original sample as calculated for the six-year period was 1.3 cases/1000 women/year whereas the prevalence by 1980-81 was 13 cases/1000 women. We conclude that a single T3 determination will in most cases be sufficient for the diagnosis of clinical hyperthyroidism in a non-hospitalized population. Our study indicates some of the problems associated with the follow-up of a general screening for hyperthyroidism, the possible benefit of which remains to be studied.     

SERUM CALCIUM CONCENTRATION IN HYPERTHYROIDISM AT DIAGNOSIS AND AFTER TREATMENT

In a large, mainly outpatient, series of hyperthyroid patients who attended a district general hospital the serum concentrations of calcium and albumin were measured before and in many cases after treatment. The calcium level (mean +/- SD) before treatment (2.41 +/- 0.21 mmol/l, n = 437) was significantly higher (P less than 0.01) than afterwards (2.36 +/- 0.15 mmol/l, n = 232) and the albumin level rose when the patients became euthyroid (from 40.5 +/- 3.1 g/l to 44.0 +/- 2.4 g/l; P less than 0.01). After treatment neither value differed from those of an unselected group of out-patients. The usual relation between the serum concentrations of calcium and albumin did not hold in the hyperthyroid subjects but reverted to normal on treatment; the variation, probably due to an increase in ionized calcium, leads to an overestimate of the 'corrected calcium' when conventional methods are used to calculate this figure. Thus, using a conventional formula 8.5% of our hyperthyroid patients would appear to have a calcium greater than 2.65 mmol/l (normal mean plus 2 standard deviations) whereas using a correction factor specific for the hyperthyroid situation the figure is reduced to 5.7% which is only twice the expected proportion. The calcium level was significantly greater (P less than 0.001) in those patients in whom initial T3 concentration was high (greater than 7.2 nmol/l). There was no effect of T4 upon serum calcium which could not be accounted for by the action of T3. In this series of 437 patients there was no case of symptomatic hypercalcaemia. The maximum value was 2.80 mmol/l in a patient with coincident primary hyperparathyroidism. Significant hypercalcaemia is rare in hyperthyroidism.     

HYPERTHYROIDISM AND THYROID CANCER

Ten of 502 patients presenting with thyroid cancer were hyperthyroid due to Graves' disease (4 patients), multinodular goitre (3), an autonomous functioning nodule (1) and a large functioning tumour (2). In addition eight patients had a past history of Graves' disease and four of hyperthyroidism associated with multinodular goitre. Mortality in patients with Graves' disease and with multinodular goitre appeared similar to that of other patients of comparable age. Both patients with large functioning tumours died from progressive disease. Concentration 131I by tumour metastases was present in one patient with active Graves' disease who had a high serum concentration of TSH-receptor binding antibodies, indicating that these antibodies may chronically stimulate tumour function. The potential for 131I concentration by tumour when TSH secretion is suppressed should therefore be determined in patients with Graves' disease and if demonstrable tumour function is present, reflecting stimulation by Graves' immunoglobulins, then elimination of tumour remnants is particularly important.     

肝炎、肝硬变胶原间质免疫电镜研究

采用免疫电镜技术对10例慢性活动性肝炎（CAH）的活检标本和3例正常肝的细胞外基质的Ⅲ、Ⅳ、Ⅵ型胶原，纤维连结蛋白（FN）和层粘蛋白（LM）进行了研究。结果发现：在CAH其迪氏腔中的Ⅲ、Ⅳ、Ⅵ型胶原，LM，FN和肝细胞之间的间隙内的FN均较正常肝增多。Ⅲ型胶原，LM和FN在CAH贮脂细胞内质网的阳性程度比正常增强。本文的结果提示迪氏腔是肝纤维化的始发部位，FN与纤维化的始发机制有关。贮脂细胞是肝纤维化时产生胶原的重要细胞。     

HYPERTHYROIDISM IN GESTATIONAL TROPHOBLASTIC NEOPLASIA

The thyroid status of twenty-seven African patients with gestational trophoblastic neoplasia (GTN) was studied. Fifteen patients were found to be biochemically hyperthyroid (eight patients with choriocarcinoma; seven with hydatidiform mole). Of these fifteen patients, nine were clinically thyrotoxic. The most serious complication of thyrotoxicosis was life-threatening acute pulmonary oedema with associated cardiac failure. It was found that when serum levels of the human chorionic gonadotrophin (hCG) reached a level of about 0·1 ± 10⁶ iu/l, thirteen of sixteen patients were biochemically hyper-thyroid; at serum levels of 0·3 ± 10⁶ iu/l of hCG most patients were clinically thyrotoxic. A feature of hyperthyroidism associated with GTN is that whereas T4 is invariably raised the T3:T4 ratio tends to be low (0·015 ± 005); rT3:T3 ratios were high in this group. TSH levels were not increased.     

VITAMIN D METABOLISM IN HYPERTHYROIDISM

The serum concentrations of 25-hydroxycholecalciferol (25 OH D₃), 24,25-dihydroxycholecalciferol [24,25(OH)₂D₃] and 1,25-dihydroxycholecalciferol [1,25(OH)₂D₃] were measured in twenty-one patients with untreated hyperthyroidism. Compared with control subjects, 25 OH D₃ concentrations were not altered, 24,25(OH)₂D₃ concentrations were increased, although not significantly and 1,25(OH)₂D₃ concentrations were decreased (P= 0.01). Following oral carbimazole therapy, 24,25(OH)₂D₃ concentrations fell (P<0.01), 1,25(OH)₂D₃ concentrations increased (P<0.01) and 25 OH D₃ concentrations were unchanged. The altered 1,25(OH)₂D₃ and 24,25(OH)₂D₃ concentrations found in hyperthyroidism are probably due to the effects of thyroid hormone on bone and mineral metabolism. Increased serum calcium and phosphate concentrations with secondary hypoparathyroidism result in stimulation of the renal 24-hydroxylase and suppression of the 1-hydroxylase enzymes. In addition, serum 24,25(OH)₂D₃ concentrations were significantly correlated with serum triiodothyronine levels (T3) (r= 0.66, P<0.002) before treatment. This may indicate a direct stimulatory effect of T3 on 24-hydroxylase activity. No relationship was found between serum 1,25(OH)₂D₃ concentrations before therapy and serum T3.     

134例甲状腺功能亢进症血清骨钙素水平的变化

对134例甲状腺功能亢进症(简称甲亢)血清骨钙素(osteocalcin,BGP)、Ca、P、AKP、桡骨及尺骨骨矿物质含量(BMC)、骨密度(BD)进行了测定。BGP水平高于相应年龄、性别的对照组(333例,P<0.01)。4.9％低血钙、6.0％低血磷、10.8％AKP升高、56％的患者BMC及BD水平降低。BGP与甲亢病程呈正相关关系,治疗前升高最显著,随病情好转逐渐降低。血清BGP测定可作为甲亢骨病的较敏感可靠的诊断指标,而AKP测定的敏感性较差。     

66例甲状腺功能亢进症患者骨质改变的临床分析

本文对66例甲亢患者测定了桡、尺骨矿物质含量(BMC)、骨密度(BD)、甲状旁腺激素(PTH)以及各种钙磷代谢的指标。50％的患者BMC和BD水平降低,44％的患者PTH水平升高。BMC和BD与病程、甲状腺肿、突眼及应用甲状腺素治疗呈相关关系。我们的初步结果表明BMC和BD的测定是甲亢骨病的一个辅助诊断指标。     

HYPERTHYROIDISM AND THE IMPALPABLE THYROID GLAND

A retrospective analysis of 594 unselected cases of hyperthyroidism from one district was made to determine whether the thyroid gland had been palpable on presentation. The thyroid had been diffusely palpable in 374 patients (63%), nodular in 110 (19%) and impalpable in 96 (16%); there was no clinical record in 14 (2%) cases. Under 40 years of age a diffuse gland was usual, being present in 86% of cases. The proportion of nodular and impalpable glands both increased progressively with age comprising 30% and 48% respectively in patients older than 70 years. Grave's ophthalmopathy was present in 13% of hyperthyroid patients with diffuse glands, in 12% of those with impalpable glands, but in only 1.5% of those with nodular thyroids. Thyroid autoantibodies were found with a similar frequency in all three groups. There was a very good correspondence between clinical assessment of shape and nodularity of thyroid and the results of isotope scanning; the majority of patients with impalpable glands (86%) had a diffuse uptake of isotope. In the elderly hyperthyroid patient an impalpable thyroid gland is common and is not a factor to weight against the diagnosis.     

SPINAL BONE MINERAL CONTENT IN MYXOEDEMA AND THYROTOXICOSIS. EFFECTS OF THYROID HORMONE(S) AND ANTITHYROID TREATMENT

The effects of thyroid hormones and antithyroid treatment upon lumbar spine bone mineral content (lumbar BMC) were studied in a consecutive series of patients with myxoedema and thyrotoxicosis, respectively. All patients were investigated in the untreated state and 3-monthly during appropriate treatment for 1 year by using dual-photon [153Gd] absorptiometry. Patients with myxoedema (n = 8) did not differ from normal individuals as regards initial lumbar BMC, but levothyroxine-treatment caused significant reduction in this variable. The median decrease in lumbar BMC after 1 year was 8.9% (95% confidence limits 1.5-15.4%, P less than 0.05). This loss of bone might be attributed to an inappropriate increase in bone turnover in the euthyroid state. It is as yet uncertain whether it predisposes to spinal osteopenia. Median lumbar BMC in patients with thyrotoxicosis (n = 25) was 12.6% (2.0-16.6%, P less than 0.05) lower than that of normal individuals before the beginning of treatment. Lumbar BMC increased during antithyroid therapy. The median gain in bone mineral after 1 year was 3.7% (1.6-9.6%, P less than 0.01). These findings suggest that excess of thyroid hormones leads to negative spinal bone mineral balance. The revealed bone loss was clinically insignificant, however, and it appeared to be at least partially reversible after antithyroid treatment.